Abstract：
Both dopamine (DA) and serotonin (5-HT) play key roles in numerous functions including motor control, stress response and learning. So far, there is scarce or conflicting evidence about the effects of 5-HT1A and 5-HT2A receptor (R) agonists and antagonists on recognition memory in the rat. This also holds for their effect on cerebral DA as well as 5-HT release. In the present study, we assessed the effects of the 5-HT1AR agonist 8-OH-DPAT and antagonist WAY100,635 and the 5-HT2AR agonist DOI and antagonist altanserin (ALT) on rat behaviors. Moreover, we investigated their impact on monoamine efflux by measuring monoamine transporter binding in various regions of the rat brain. After injection of either 8-OH-DPAT (3 mg/kg), WAY100,635 (0.4 mg/kg), DOI (0.1 mg/kg), ALT (1 mg/kg) or the respective vehicle (saline, DMSO), rats underwent an object and place recognition memory test in the open field. Upon the assessment of object exploration, motor/exploratory parameters and feces excretion, rats were administered the monoamine transporter radioligand N-o-fluoropropyl-2b-carbomethoxy-3b-(4-[123I]iodophenyl)-nortropane ([123I]-FP-CIT; 8.9 ± 2.6 MBq) into the tail vein. Regional radioactivity accumulations in the rat brain were determined post mortem. Compared vehicle, administration of 8-OH-DPAT impaired memory for place, decreased rearing behavior, and increased ambulation as well as head-shoulder movements. DOI administration led to a reduction in rearing behavior but an increase in head-shoulder motility relative to vehicle. Feces excretion was diminished after ALT relative to vehicle. Dopamine transporter (DAT) binding was increased in the caudateputamen (CP), but decreased in the nucleus accumbens (NAC) after 8-OH-DPAT relative to vehicle. Moreover, DAT binding was decreased in the NAC after ALT relative to vehicle. Findings indicate that 5-HT1AR inhibition and 5-HT2AR activation may impair memory for place. Furthermore, results imply associations not only between recognition memory, motor/exploratory behavior and emotionality but also between the respective parameters and the levels of available DA in CP and NAC.
摘要：
多巴胺（DA）和5-羟色胺（5-HT）在许多功能中起关键作用，包括运动控制，应激反应和学习。到目前为止,关于5-HT1A和5-HT2A受体(R)激动剂和拮抗剂对大鼠识别记忆的影响的证据很少或相互矛盾.这也适用于它们对脑DA以及5-HT释放的影响。在本研究中,我们评估了5-HT1AR激动剂8-OH-DPAT和拮抗剂WAY100,635以及5-HT2AR激动剂DOI和拮抗剂altanserin（ALT）对大鼠行为的影响。此外，我们通过测量大鼠大脑各个区域的单胺转运体结合，研究了它们对单胺外排的影响。注射8-OH-DPAT（3mg/kg）后，WAY100,635(0.4mg/kg),DOI（0.1mg/kg），ALT（1mg/kg）或各自的载体（盐水，DMSO),大鼠在开放领域进行了物体和地点识别记忆测试。在评估对象勘探时，运动/探索参数和粪便排泄，大鼠尾静脉给药单胺转运蛋白放射性配体N-o-氟丙基-2b-碳甲氧基-3b-（4-[123I]碘苯基）-去甲氨烷（[123I]-FP-CIT；8.9±2.6MBq）。死后确定大鼠大脑中的区域放射性积累。与对照相比，施用8-OH-DPAT受损的记忆，饲养行为减少，增加了步行和头肩运动。DOI给药导致饲养行为减少，但头肩运动性相对于载体增加。相对于媒介物,ALT后粪便排泄减少。多巴胺转运体（DAT）结合在尾果核（CP）中增加，但相对于载体，8-OH-DPAT后伏隔核（NAC）减少。此外，相对于载体,ALT后NAC中的DAT结合降低。研究结果表明，5-HT1AR抑制和5-HT2AR激活可能会损害对位置的记忆。此外，结果不仅意味着识别记忆之间的关联，运动/探索行为和情绪，以及相应的参数和CP和NAC中可用DA的水平之间的关系。
